Twenty-two mouse myeloma kappa light chains (designated V kappa 21) have been found to have cross-reacting idiotypes. The pattern of diversity among these structurally similar kappa chains will be determined by amino acid sequence analysis in order to further define the genetic basis of antibody diversity. These kappa chain sequences offer a unique opportunity to reconcile conflicting theories of antibody diversity which have been proposed from the nucleic acid hybridization data and the amino acid sequence data. These sequences will permit an identification of the structural basis of idiotype by determining the major framework antigenic determinants by which these light chains can be serologically identified. Since these V kappa 21 idiotypes can be detected on about 10% of normal serum immunoglobulins, the idiotypes can be used to explore the specificity and control of the anti-idiotype network which is thought to control levels of humoral antibody. The V kappa 21 idiotype antisera will also be utilized to determine the extent to which combinatorial association generates antibody diversity. The antigen binding Igs with the V kappa 21 idiotype will be used to make hybrid Igs with each of the V kappa 21 light chains. Antigen binding data of the hybrid molecules will be compared with known Ig structures to determine how light chain substitutions modify the antigen binding site.